The NHGRI Division of Intramural Research maintains a robust computational infrastructure for specialized research computing. These resources are provided to support the Division's broad program of genomic, bioinformatic, clinical, and behavioral research aimed at translating genomic and genetic research into a greater understanding of human genetic disease, as well as towards developing better methods for the detection, prevention and treatment of heritable and genetic disorders. NHGRI/DIR maintains several high-end computer systems to support state-of-the-art computational sequence analysis, structure analysis, and similar memory-intensive scientific computing. The Division also provides significant computational resources in support of its high-throughput research efforts in whole-genome sequencing, whole-genome association studies, and similar types of genome-wide analyses. In the last year, we have placed particular emphasis on the infrastructure required to store and analyze "next-generation" sequencing data. These approaches generate enormous amounts of data (on the order of terabytes) in a single run, thereby requiring strong database solutions, innovative storage and archiving strategies, and a reliable high-performance computing environment. NHGRI/DIR maintains an extensive suite of commercial and public domain software for handling the wide range of needs of NHGRI investigators. The list includes software for DNA and protein sequence analysis, molecular modeling, microarray analysis, pathway analysis, biostatistics, and the analysis of data being generated by whole-genome association studies. In addition, realizing the importance of providing NHGRI scientists with a first-rate database for clinical research, a Web-based and HIPAA-compliant database with an integrated pedigree viewer and SQL querying tool is made available to all NHGRI investigators conducting clinical protocols aimed at understanding the underlying mechanisms of a wide variety of human genetic disorders. This clinical databases functionality allows for the automated import of clinical laboratory data from the NIH Clinical Center's Clinical Research Information System (CRIS) database.